論文 - 詳細
| RRC ID | 62027 |
|---|---|
| 著者 | Vong LB, Mo J, Abrahamsson B, Nagasaki Y. |
| タイトル | Specific accumulation of orally administered redox nanotherapeutics in the inflamed colon reducing inflammation with dose-response efficacy. |
| ジャーナル | J Control Release |
| Abstract |
Although current medications for ulcerative colitis (UC) are effective to some extent, there are still some limitation of their use due to the non-specific distribution, drug metabolism in the gastrointestinal tract, and severe adverse effects. In our previous studies, we developed oral redox nanoparticles (RNP(O)) that specifically accumulated and scavenged overproduced reactive oxygen species (ROS) in an inflamed colon. However, the mechanism leading to specific accumulation of RNP(O) in an inflamed colon is still unclear. In this study, we investigated the cellular uptake of RNP(O) into ROS-treated epithelial colonic cells in vitro, and compared to the untreated cells, found a significantly increased uptake in ROS-treated cells. In vivo, we discovered that orally administered RNP(O) were not internalized into the cells of a normal colon. A significant amount of disintegrated RNP(O) was detected in the cells of an inflamed colon of dextran sodium sulfate (DSS)-induced colitis mice, resulting in scavenging of ROS and suppression of inflammation with low adverse effects. Furthermore, we confirmed a significant reduction of disease activity and a robust dose response efficacy following RNP(O) treatment in acute DSS-induced colitis mice, outperforming the positive control 5-aminosalicylic acid. Oral administration of RNP(O) is a promising approach to develop a new therapy for UC disease. |
| 巻・号 | 210 |
| ページ | 19-25 |
| 公開日 | 2015-7-28 |
| DOI | 10.1016/j.jconrel.2015.05.275 |
| PII | S0168-3659(15)00574-X |
| PMID | 25998050 |
| MeSH | Administration, Oral Animals Anti-Inflammatory Agents / pharmacology Anti-Inflammatory Agents / therapeutic use* Caco-2 Cells Colitis, Ulcerative / chemically induced Colitis, Ulcerative / drug therapy* Colitis, Ulcerative / metabolism Colitis, Ulcerative / pathology Colon / drug effects Colon / pathology Dextran Sulfate Dose-Response Relationship, Drug Humans Hydrogen Peroxide / pharmacology Interleukin-8 / metabolism Leukocyte L1 Antigen Complex / metabolism Male Mice Mice, Inbred ICR Nanoparticles / therapeutic use* Oxidants / pharmacology Oxidation-Reduction |
| IF | 7.727 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |